PDBsum entry 5cra

Hydrolase

PDB id: 5cra

Contents

Protein chains

172 a.a.

75 a.a.

Ligands

SO4 ×9

GVE ×2

Waters ×32

PDB id:

5cra

Name:

Hydrolase

Title:

Structure of the sdea dub domain

Structure:

Sdea. Chain: a, b. Fragment: dub domain (residues 6-198). Engineered: yes. Polyubiquitin-b. Chain: d, c. Fragment: unp residues 1-75. Engineered: yes

Source:

Legionella pneumophila. Organism_taxid: 446. Expressed in: escherichia coli. Expression_system_taxid: 511693. Homo sapiens. Human. Organism_taxid: 9606. Gene: ubb. Expression_system_taxid: 562

Resolution:

2.64Å R-factor: 0.187 R-free: 0.236

Authors:

M.J.Sheedlo,J.Qiu,Z.Q.Luo,C.Das

Key ref:

M.J.Sheedlo et al. (2015). Structural basis of substrate recognition by a bacterial deubiquitinase important for dynamics of phagosome ubiquitination. Proc Natl Acad Sci U S A, 112, 15090-15095. PubMed id: 26598703 DOI: 10.1073/pnas.1514568112

Date:

22-Jul-15 Release date: 25-Nov-15

Protein chains

Q6RCR0  (Q6RCR0_LEGPN) -  SdeA from Legionella pneumophila

Seq: 1504 a.a.

Struc: 172 a.a.

Protein chains

P0CG47  (UBB_HUMAN) -  Polyubiquitin-B from Homo sapiens

Seq: 229 a.a.

Struc: 75 a.a.

DOI no: 10.1073/pnas.1514568112

Proc Natl Acad Sci U S A 112:15090-15095 (2015)

PubMed id: 26598703

Structural basis of substrate recognition by a bacterial deubiquitinase important for dynamics of phagosome ubiquitination.

M.J.Sheedlo, J.Qiu, Y.Tan, L.N.Paul, Z.Q.Luo, C.Das.

ABSTRACT

Manipulation of the host's ubiquitin network is emerging as an important strategy for counteracting and repurposing the posttranslational modification machineries of the host by pathogens. Ubiquitin E3 ligases encoded by infectious agents are well known, as are a variety of viral deubiquitinases (DUBs). Bacterial DUBs have been discovered, but little is known about the structure and mechanism underlying their ubiquitin recognition. In this report, we found that members of the Legionella pneumophila SidE effector family harbor a DUB module important for ubiquitin dynamics on the bacterial phagosome. Structural analysis of this domain alone and in complex with ubiquitin vinyl methyl ester (Ub-VME) reveals unique molecular contacts used in ubiquitin recognition. Instead of relying on the Ile44 patch of ubiquitin, as commonly used in eukaryotic counterparts, the SdeADub module engages Gln40 of ubiquitin. The architecture of the active-site cleft presents an open arrangement with conformational plasticity, permitting deubiquitination of three of the most abundant polyubiquitin chains, with a distinct preference for Lys63 linkages. We have shown that this preference enables efficient removal of Lys63 linkages from the phagosomal surface. Remarkably, the structure reveals by far the most parsimonious use of molecular contacts to achieve deubiquitination, with less than 1,000 Å(2) of accessible surface area buried upon complex formation with ubiquitin. This type of molecular recognition appears to enable dual specificity toward ubiquitin and the ubiquitin-like modifier NEDD8.